Abstract:
Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
摘要:
自闭症谱系障碍(ASD)被报道为一组神经发育障碍。在自闭症患者和患有ASD危险基因功能障碍的小鼠模型中,广泛报道了包括海马在内的大脑区域的结构变化。但是潜在的机制还没有完全理解。这里,我们报告删除三重奏,自闭症的高易感基因,导致出生后齿状回(DG)发育不全,带有锯齿状锥体外系刀片,三重奏缺陷小鼠表现出自闭症样行为。DG的形态发生受损主要是由于有丝分裂后颗粒细胞(GC)的出生后分布受到干扰,这进一步导致神经祖细胞的迁移缺陷。此外,我们通过空间转录组测序揭示了Trio在各种兴奋性神经细胞中发挥不同的作用,特别是调节有丝分裂后GCs迁移的作用。总之,我们的发现提供了Trio参与出生后DG形态发生的细胞机制的证据.